Abstract
Pentaminomycins C–E (1–3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino acid, N5-hydroxyarginine, based on 1D and 2D NMR and mass spectroscopic analyses. The absolute configurations of the amino acid residues were assigned using Marfey’s method and bioinformatics analysis of their nonribosomal peptide biosynthetic gene cluster (BGC). Detailed analysis of the BGC enabled us to propose that the structural variations in 1–3 originate from the low specificity of the adenylation domain in the nonribosomal peptide synthetase (NRPS) module 1, and indicate that macrocyclization can be catalyzed noncanonically by penicillin binding protein (PBP)-type TE. Furthermore, pentaminomycins C and D (1 and 2) showed significant autophagy-inducing activities and were cytoprotective against oxidative stress in vitro.
Highlights
Microbial secondary metabolites have been utilized for the discovery and development of innumerable medicinal drugs, such as antibiotics, anticancer agents, and immunosuppressive medicines [1]
Studying the metabolites of insect-associated actinomycetes led to the discovery of the new cyclic depsipeptide dentigerumycin [4], a geldanamycin analog natalamycin [5], the polyketide alkaloid camporidine A [6], N-acetylcysteamine-bearing indanone thioester formicin A [7], and chlorinated cyclic peptides, nicrophorusamides [8]
Further analysis of the NMR spectra (Figures S1–S5) confirmed this compound as the previously reported cyclic peptide, pentaminomycin C [18], which consists of five amino acids: leucine, valine, tryptophan, N5 -hydroxyarginine, and phenylalanine
Summary
Microbial secondary metabolites have been utilized for the discovery and development of innumerable medicinal drugs, such as antibiotics, anticancer agents, and immunosuppressive medicines [1]. Studying the metabolites of insect-associated actinomycetes led to the discovery of the new cyclic depsipeptide dentigerumycin [4], a geldanamycin analog natalamycin [5], the polyketide alkaloid camporidine A [6], N-acetylcysteamine-bearing indanone thioester formicin A [7], and chlorinated cyclic peptides, nicrophorusamides [8]. These bacterial secondary metabolites display antifungal, Microorganisms 2020, 8, 1390; doi:10.3390/microorganisms8091390 www.mdpi.com/journal/microorganisms
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